DESCRIPTION (Applicant's Abstract): Dr. Wenner, a conventionally-trained Immunologist, seeks to broaden her knowledge base and acquire new skills in the important and emerging field of botanical medicine research. She plans to establish herself as an independent researcher in this new field, conducting innovative and timely studies correlating composition with immunomodulatory activities to rigorously assess botanical medicines for clinical application to immune-related disorders. Her career development plan includes didactic and technical training in three critical areas: botanical medicine, natural products analytical chemistry, and medicinal chemistry. Dr. Wenner has brought together an experienced interdisciplinary team of two co-sponsors to assist her in this training. Her main sponsor, Gowsala Sivam, PhD, Senior Investigator, Bastyr University Research Institute, has extensive expertise in natural products and biomedical research. Dr. Wenner's cosponsor, Professor Gary Elmer, University of Washington School of Pharmacy, is a well-established researcher in the area of medicinal chemistry. During the five-year award period, Dr. Wenner will conduct research investigating the correlation between formulation composition and bioactivity of a popular botanical medicine, Echinacea. This leading herbal remedy is available over the counter in the U.S. and has reported effectiveness in combating upper respiratory infections (URIs). Many types of preparations are available on the market, without adequate correlation of composition with reported immunomodulatory activities. Which of these formulations is best suited to treat a particular health condition is thus unknown. Importantly, composition of Echinacea preparations, being a natural product, varies significantly with different species, plant part, harvesting times, storage conditions and extraction procedures. An immediate need exists to rigorously assess how Echinacea composition correlates with immunological activities to help elucidate mechanism of action and accurately assess the potential for safety and effectiveness in its clinical application. Additionally, whether in vivo bioactivation occurs to generate hepatic metabolites having immunomodulating activities is currently unknown and will be addressed using an in vitro hepatic metabolism model. Herb/drug interactions also will be important to evaluate, since individuals taking commonly prescribed conventional drugs often concurrently use Echinacea. Since many of these drugs interact with the hepatic cytochrome P450 (CYP) isoenzymes involved in drug metabolism, Echinacea's effects on drug-induced inhibition of CYP isoenzyme activity will be determined. By addressing these aims, Dr. Wenner will gain strong research skills in botanical medicine and the expertise necessary to significantly impact this field.